This study is designed to assess possible genetic factors influencing antibody responses to H. influenzae type b and meningococcal group C polysaccharide vaccines. The study population will be siblings of patients with Haemophilus influenzae type b meningitis or epiglottitis, and control children. Immune response (Ir) genes have been defined in laboratory animals which are linked to the major histocompatibility complex, or to immunoglobulin (Ig) allotypes. We propose to determine certain HLA serological determinants and Ig allotypes in patients with Haemophilus influenzae type b meningitis or epiglottitis. The frequencies of these genetic determinants will be compared to those present in uninfected siblings, and in control children without a family history of diseases caused by Haemophilus influenzae. A randomized, comparative study of Haemophilus influenzae type b and meningococcal group C polysaccharide vaccines will be conducted in siblings and in control children. The responses to the vaccines in two groups will be compared, and we will attempt to determine if there is any association between the magnitude of the antibody responses and the genetic markers under study. Our hypothesis is that the siblings are at increased risk of infection, in part, because of genetic factors. If this is true, we predict that they will show evidence of impaired antibody responses to immunization, particularly those with identical HLA or Ig allotype haplotypes as their infected siblings. The results of this study may help identify Ir genes in humans which regulate antibody concentrations to bacterial polysaccharides. The data also may have important implications for the design of future trials assessing the efficacy of polysaccharide vaccines.